Process for the manufacture of 2-cyanoethylated n-substituted imines



United P MQ? PROCESS FOR THE MANUFACTURE OF Z-CYANO- ETHYLATED N-SUBSTITUTED IMINES Heinrich Krimm, Krefeld-Uerdingen, Germany, assignor to Farbenfabriken Bayer Aktiengesellschaft, Leverkusen, Germany, a corporation of Germany No Drawing. Application August 10, 1954, Serial No. 448,999

Claims priority, application Germany August 24, 1958 I 16 Claims. (Cl. 260-464) The present invention comprises a process for the manufacture of 2-cyanoethylated N-substituted imines.

I According to the invention Z-cyanoethylated N-substituted imines are obtained fromrN-substi-tuted aldoimines or ketoimines with at least one hydrogen atom on the cacarbon atoms, by conversion with acrylonitrile. The

hydrogen atoms standing in 2-positionof the imines. are

react with acrylonitrile without catalysts. This shows that the conversion of aldehydes with acrylonitrile is practically without significance, because the aldehydes, in the necessarily strongly alkaline reaction, easily escape the desired conversionby aldol condensation.

In the reaction with ketones, when these are present in excess, preponderantly all activated hydrogen atoms 2,768,962 Patented Oct. 30,

ice

The N-substituted imines suitable for the present invention can be obtained in known manner by the condensation of aliphatic, cycloaliphatic, araliphatic or aromatic primary a1nines.

Suitable aldehydes are for example acetaldehyde, propionaldehyde, n-butyraldehyde, isobutyraldehyde, n-valeraldehyde, isovaleraldehyde, capronaldehyde, enathaldehyde, succindialdehyde, formylcyclohexane, phenylacetaldehyde and hydrocinnamic aldehyde. d

Suitable ketones are for example acetone, methylethyl ketone, m'ethyl-n-propyl ketone, diethyliketone, methylisobutyl ketone, methyl-n-amyl ketone, ethyl-n butyl ketone, methyl-n-heptyl ketone, diisobutyl lcetone, methyl te-rt.butyl ketone, acetyl acetone, acetonyl acetone, a ceto-j phenone, propiophenone, cyclopentanone, cyclohexanonej, 1-methylcylclohexanone-2, 1-cyclohexy1-cycl-ohexanon-Z, cycloh'exandi'one- 1,4, acetyl-cyclohexanone, d-hydrindone, and u-tetralone. I

Suitable amines are for example methylamine, ethylamine, n-propylamine, isopropylamine, n-butylamine, sec.-butylamine, tertbutylamine', isobutylamine, isoamylamine, n-dodecylamine, ethylendiamine, hexamethylendi- Whereas aldehydes and ketones react with on*=some of the total available ketone molecules are reagainst this, the imines react with 'acr'ylonitrile in stages. With an excess of imine firstly one hydrogen atom will react in each available imine molecule, then a'-: se'c ond hydrogen atom and so on, so that, according to the proportions and reaction conditions, mono-cyanoethyl- 5 ated, di-cyanoethylated"imines and so on, can be obtained in a smooth reaction as main products. The present method therefore offers the advantagethat partially cyanoethylated imines can-jbeproducediin a good yield.

As a rule, the. ketoim'ines are only capable of adding, per mol, 1 mol of acrylonitrile on one and the same carbon atom, whilst the aldoimines add in stages as many mols of acrylonitrile per carbon' atom-a s hydrogen atoms are available on them. In the case of'a'cetaldoimines all ii-hydrogen atoms of the 2-carbon atom can therefore be replaced byi'cyanoethyl residues. From ketoimines there can thus be obtained 2-monoor 2,2-dicyanoethylated ketoimines, from aldoim'ines 2'-mono-, 2,2-dior 2,2,2- tricyanoethylated aldoimines as main, reaction products.

;'I"he"ne wcompoundsar'e valuable.intermediateiproducts for agreat varietylof organic syntheses. Thus, it is possible for example to produce monoor bifunctiona'l amines;

by hydrogenation, the corresponding Z -cyanOethylated aldehydes or ketones by cautiousghydrblysis, and monoor bifnnctional formyl-carb oxylic acids orketocarboxylic acids T by energetic 1 hydrolysis, from which polycarboxylic acids may be obtained by oxidation-if'desired. The production of ketodicarboxylic acids is of 'special practical importance, because, for the above reasons, there are no other *technically satisfactory processes via synthesis of cyanoethylated ketones.

the direct v amine, cyclopentylamine, cyclohexylarnine, 4 methylcyclohexylamine,lbenzylamine, aniline, -o'-, m-, p-toluidine, 0-, m-, p-chloraniline, 0;, m-, p-nitroaniline, benzidine and p-anisidine. I i According to the'invention, theimine is heated'lto ithe necessary reaction temperature in mixture with an amount of acrylonitrilesuflicient "to form the desired reaction product. Sometimes it is advantageous to use morej'or less acrylonitrile than theoretically required. 7, sati sfactdry yields are often obtained by introducing'the acrylonitrile into the imine at the reaction temperature, while stirring.

When adding one mol of acrylonitrile on one carbon atom, conversion is in general possible-at normal pressure, because temperatures of for example from about 20". C. to about 150 C. are in most cases sufficient. The higher cyanoethylating stages on one carbonfatom may however only beachieved at temperatures of from about C. to 250. -C., and corresponding pressures, in autoclaves; Apart fromthis, the mostfavourable temperature depends on the structure of the imine. Ketoimines. for example which derive from aromatic amines, :req-u i re .in "general higher reaction temperatures than those of-.-th e .aliphatic or cycloaliphatic amine series. The most suitable tern perature and pressure range can easily be established in each case by preliminary experiments.

It is possible to accelerate the reaction by catalysts. Suitable catalysts are basically acting compounds, such as alkali hydroxide or alkaline earth hydroxide, quaternary ammonium basesyfor exampletrirnethylbenzyl-ammonium hydroxide or triethylbenzyl-ammonium hydroxide, .aswell as high-molecular quaternary ammonium In order; to avoidjthe polymerization of -the"{acrylo i nitrile'dufing the reactiongit isii'n mos ,c sesf advanta geous toadd a small amount of apolymerizatioij inhibitor; such iasj' e. .hydroquinone, t ert.butylpyrocatechol. r m lu e- 1 1 1 a Thefollowing examples are 'given fdr the purpose illustrating the invention. i l

Example '1 distillation. 752 of 2 (fi cyanoethyl) N cycldliexyf n-bu'tyraldoimine are obtained at 108-112C./0.2 mm. Hg. Yield: 73% of the theoretical. CiaHzzNa (206.3):

Found, Calculated, percent percent C=75. 24 C=75. 67 H=10. 79 H=10. 75 N=13. 41 N=13. 58

Example 2 64 gm. (1.2 mol) of acrylonitrile are introduced into a mixture of 153 gm. (1 mol) N-cyclohexyl-n-butyraldoimine, 1 gm. of triethylbenzyl ammonium hydroxide and 0.1 gm. of hydr-oquinone and the mixture is heated to boiling until the temperature has reached 150 C. By distilling the reaction product in vacuo there are obtained at 150-153" C./10 mm. Hg 165 gm. of 2-(5- cyanoethyl)-N-cyclohexyl-n-butyraldoimine. Yield: 80% of the theoretical.

Example 3 A mixture of 765 gm. (5 mol) of N-cyclohexyl-n- 'b'utyraldoimine and 530 gm. mol) of acrylonitrile is heated in an autoclave in a nitrogen atmosphere of initially 1 atm. pressure to 200 C., until the pressure has decreased from 8 atm. to 3.5 atm. The brownish reaction product which crystallizes on cooling, is purified by re-crystallization from light petroleum or cyclohexane. 906 gm. of 2,2-di-(f3-cyanoethyl)-N-cycloheXyl-n-butyraldoimine of melting point 6364 C. are obtained. Yield: 70% of the theoretical.

C16H25N3 (259.4):

Found, Calculated, percent percent C=73. 91 O=74. 08 H= 9.70 H= 9.72 N=15. 97 N=16. 20

The structure of the 2,2-di-(p-cyanoethyl-N-cyclohexyl-n-butyraldoimine is confirmed by saponification with dilute sulphuric acid which yields 2,2-di-(fl-cyanoethyl)-n-butyraldehyde having a boiling point of 168- 170" C./0.2 mm. Hg, from which my hydrolysis and oxidation with a mixture of concentrated sulphuric acid and nitric acid 'y-carboxy-y-ethyl-pimelic acid with melting point l70171 C. is produced. This is identical with the tricarboxylic acid prepared by H. A. Bruson and T. W. Riener :by another method (Am. Soc. 64, 2856 (1942)).

Example '4 :A mixture of 195 gm. (1 mol) of N-cyclohexyl-enanthaldoimine, 64 gm. (1.2 mol) of acrylonitrile and 0.3 gm. ofhydroquinone is heated in an autoclave in a nitrogen atmosphere initially of 1 atm. to 150 C., until the pressurehas dropped to aconstant value. The brown reactionmixture is worked up by vacuum distillation. 149

gm. of 2-(B-cyanoethyl)-N-cyclohexyl-enanthaldoimine are obtained at 190194 C./0.4 mm. Hg. Yield: 60% of the theoretical.

CwHzsNz (248.4):

Found, Calculated, percent percent O=77. 22 0:77.36 H=11. 25 H=11.36 N=11. 37 N=11. 28

Example 5 A mixture of 125 gm. (1 mol) of N-cyclohcxylacetaldoimine, 159 gm. (3 mol) of acrylonitrile and 1 gm. of hydroquinone is heated in an autoclave in a nitrogen atmosphere of initially 1 atm. to 200 C., until the pressure has been reduced from 8 atm. to 4 atm. The reaction product which on cooling partly crystallizes, is recrystallized from toluene. 114 gm. of 2,2,2-tri-(fl-cyanoethyl)-N-cyclohexyl-acetaldoimine with melting point l09-l10 C. are obtained. Yield: 40% of the theoretical. C17H24N4 (284.4):

Found, Calculated, percent percent O=71. 36 C=71. 79 H= 8.79 H= 8.51 N=19. 45 N=19. 70

Example 6 26.5 gm. /2 mol) of acrylonitrile stabilized with 25 mgm. of hydroquinone are added drop by drop to 89.5 gm. /2 mol) of N-cyclohexyl-cyclohexanonimine with vigorous stirring at C. in the course of 1 /2 hours. The temperature is subsequently slowly raised to 150 C., until no further reflux of boiling acrylonitrile can be observed. The reaction product is distilled in vacuo. After the brief first runnings, 91 gm. of N-cyclohexyl-Z- (,B-cyanoethyl)-cyclohexanonimine are obtained at 122 C./0.2 mm. Hg, as a yellowish oil. Yield: 78% of the theoretical. I C1sHz4Nz (232.4):

Found, Calculated, percent percent O=77. 25 O=77.63 H=10. 51 H=l0. 41 N=11. 94 N=12. 06

The compound is soluble in acids and can be hydrolized by heating for 1 hour with an excess of mineral acid to Z-(fl-cyanoethyl)-cyclohexanone (boiling point 9698 C./ 0.5 mm. Hg) and cyclohexylamine.

Example 7 53 gm. (1 mol) of acrylonitrile stabilized with, 50 mgm. of hydroquinone are added drop by drop to 89.5 gm. /z mol) of N-cyclohexyl-cyclohexanoniminewith stirring at C. in the course of 2 hours. The mixture is then heated for another 2 hours to' C., until no further reflux of boiling acrylonitrile can be observed. By vacuum distillation of the reaction product there are obtained, after the first runnings consisting of N-cyclohexyl-2-(p-cyanoethyl) cyclohexanonimine, 113 gm. of N-cyclohexy1-2,6 di-(fi-cyanoethyl)'cyclohexanonimine at 200- 205 C./0.2 mm. Hg, as a thick, yellowish oil. Yield: 79% of the theoretical.

dicyanoethylat'ed-ketoimine is also'soluble' in acids and can be saponified with' an excessof mineral'acid by heating for 1 hour to 100 C. to12,6-c li- (-fi-cyanoethy l)- e qhaanene a i s t e mel Pain 7 Example 8 51 gm. (A mol)"of'N ii butyhcyclohexanonimine are treated with 1 7.7. gm! mol); of acrylonitrile stabilized with 2Q mgrn. of hydroquinone,. and slowly heated to 150 C. until no further reflux of unreacted acrylonitrile can be observed. By the vacuum distillation of .the reaction product 48 grnfof N n-butyI Z-KB-cyanOethYD- cyclohexanonimine are obtained at 116-118 C./ 0.9 mm. Hg as a pale oil. Yield: 74% of the theoretical. C12H22N2 (194.3):

Found, Calculated, percent percent O=74. 38 O=74. 17 H=1L 25 H=11. 41 N=- 14. 65 N- 14. 42

Example 9 86.5 gm. /2 mol) of N-phenyl-cyclohexanonimine are heated with 26.5 gm. mol) of acrylonitrile containing 25 mgm. of hydroquinone for 2 hours to 100 C., for 3 hours to 130 C. and finally to 150 C., until no further reflux of boiling acrylonitrile can be observed. By the vacuum distillation of the reaction product there are obtained 70 gm. of N-phenyl-2-(fi-cyanoethyl)-cyclohexanonimine at 166-168 C./03 mm. Hg as a yellowish oil. Yield: 63% of the theoretical.

C15H18N2 (226.3)

Found, Calculated, percent percent C==79.45 O=79. 60 H= 7. 82 H= 8. 02 N=12.60 N=12.38

This cyanoethylated ketoimine can also be saponified in a smooth reaction to Z-(B-eyanoethyl)-cyclohexanone.

Example 10 56.4 gm. /3 mol) of N-cyclohexyl-methyl-n-propyl- 7 mol) of Found, Calculated,

percent percent 0:76. 25 O=76. 31 11:10. 69 H=10. 98 N==13. 02 N=12. 71

This cyanoethylated ketoimine can also be saponified to 3-(p-cyanoethyD-pentanone-2 having the boiling point 126-129 C./ 18 mm. Hg.

I claim:

1. A compound selected from the group consisting of aldoimines and ket'oimines. an tX-CaIbOII atom thereof having'at least one fi-cyanoethyl group substituent, the remaining valencies of each a-carbon atom being satisfied by a substituent-selected from the group consisting of hydrogen, mono-valent hydrocarbon radicals, and fl-cyanoethyl' -groups,' and a mono-valent hydrocarbon substituent satisfying a nitrogen atom valency of the imine'group'. 1

Comp'ounds'selected from the group consisting of mono-cyanoethylated "aldoimines, polycyanoethylated aldoimines, mono-cyanoethylated ketoimines and 2,2'-dicyanoethylated ketoimines, each cyanoethylated substituent satisfying an a-carbon atom valency with the remaining 'valencies'ofeach u-carbon atom satisfied by a' substituent sele'cted from the group consisting of hydrogen andmono valent hydrocarbon radicals, and a mono- \fale nthydrocarbon substituent satisfying a nitrogen atom valency of the'lmine group. I

3. A mono-cyanoethylated aldoimine containing a fl-cyanoethyl group on the a-carbon atom with the remaining valencies of the a-carbon atom satisfield by a substituent selected from the group consisting of hydrogen and mono-valent hydrocarbon radicals, and a mono-valent hydrocarbon substituent satisfying a nitrogen atom valency of the imine group.

4. A polycyanoethylated aldoimine containing at least two B-cyanoethyl groups on the a-carbon atom with any remaining valency of the u-carbon atom satisfield with a substituent selected from the group consisting of hydrogen and mono-valent hydrocarbon radicals, and a mono-valent hydrocarbon substituent satisfying a nitrogen atom valency of the imine group. I

5. A mono-cyanoethylated ketoimine having a B-cyanoethyl group on one a-carbon atom with the remaining valencies of the a-carbon atoms satisfield with substituents selected from the group consisting of hydrogen and monovalent hydrocarbon radicals, and a mono-valent hydrocarbon radical satisfying a nitrogen atom valency of the imine group.

6. A 2,2-dicyanoethylated ketoimine having a ,B-cyanoethyl group on each m-carbon atom with the remaining valencies of the a-carbon atoms satisfied by a substituent selected from the group consisting of hydrogen and monovalent hydrocarbon radicals, and a mono-valent hydrocarbon substituent satisfying a nitrogen atom valency of the imine group.

7. A process for the production of Z-cyanoethylated N-substituted imines which comprises reacting acrylonitrile with a compound selected from the group of imines consisting of aldoimines having at least 2 hydrogen substituents on the u-carbon atom with the remaining u-carbon atom valency satisfied by a substituent selected from the group consisting of hydrogen and mono-valent hydrocarbon radicals and ketoimines with at least one oc-carbon'atom hydrogen substituent with the remaining valencies of the a-carbon atoms satisfield by a substituent selected from the group consisting of hydrogen and mono-valent hydrocarbon radical a mono-valent hydrocarbon substituentsatisfying' a nitrogen atom valency of the imine group of the selected imine.

8. Process for the production of Z-cyanoethylated N-s'ubstituted imines according to claim 7 wherein the ratio of the amounts of imine to acrylonitrile is about 1:1 mol. p 9. Process for the production of Z-cyanoethylated N-substituted imines according to claim 7 wherein the ratio of the amounts of imine to acrylonitrile is about 1:2 mols.

10. Process for the production of 2-cyanoethylated N-substituted imines which comprises reacting an acetoaldoimine with a mono-valent hydrocarbon group at the 7 nitrogen atomwith acrylonitrile, the ratio ofthe amounts of imine to acrylonitrile being about 1:3 mols.

11. Process for the production of 2(B-cyanoethyD-N- cycloheXyl-n-butyraldoimine which comprises heating a mixture of N-cyclohexyl-n-butyraldoimine with aCrylonitrile the ratio of the amounts being about 1 molzl mol in' the presence of a little amount of hydroquinone in an autoclave under nitrogen pressure at 150 C.

12. Process for the production of 2(}8-cyanoethyl)- N-cyclohexyl-n-butyraldoimine which comprises 1 adding to a mixture of N-cyclohexyl-n-butyraldoimine, a little amount of tri-ethyl-benzyl-ammonium-hydroxide and by droquinone, acrylonitrile drop by drop the ratio of the amount of N-cyclohexyl-n-butyraldoirnine and acrylonitrile being about 1 molzl mol at about 150 C. under atmospheric pressure.

13. Process for the production of 2,2-di-(fi-cyanoethyU- N c'ycl'ohexyl-n-butyraldoimine which comprises heating a mixture of N-cyclohexyl-n-butyraldoimine and acrylonitrile the ratio of the amounts being about 1 mol:2 mols, in an autoclave under nitrogen pressure at about 200 C.

14. Process for the production of N-cyclohexyl-Z-(ficyanoethyl)-cyclohexanonimine which ,comlprises adding acrylonitrile with a little amount of hydroquinone drop by drop to N-cyclohexyl-cyclohexanonimine at temperatures from about C. to about 150 C. the ratio of the amounts of N-cyclohexyl-cyclohexanonimine and acrylonitrile being about 1 molzl mol.

15. Process for the productio'n of N-cyclohexyl-2,6- di-(fi-cyanoethyl)-cyclohexanonimine which comprises adding acrylonitrile with a little amount of hydroquinone drop by drop-to N-cyelohexyl-cyclohexanonimine at temperatures from, about C. to about C. the ratio of .N-cyclohexyl-cyclohexanonimine and acrylonitrile being about 1 mol:2 mols.

16. Z-(fi-cyanoethyl) -N-cyclohexyl-n-butyraldoimine.

References Cited in the tile of this patent.

STATES PATENTS Bruson et a1. July 18, 1944 Bruson Oct". 9, 19 45 Bruson et a1 Feb. 12, 1946 

1. A COMPOUND SELECTED FROM THE GROUP CONSISTING OF ALDOIMINES AND KETOIMINES, AN A-CARBON ATOM THEREOF HAVING AT LEAST ONE B-CYANOETHYL GROUP SUBSTITUENT, THE REMAINING VALENCIES OF EACH A-CARBON ATOM BEING SATISFIED BY A SUBSTITUENT SELECTED FROM THE GROUP CONSISTING OF HYDROGEN, MONO-VALENT HYDROCARBON RADICALS, AND B-CYANOETHYL GROUPS, AND A MONO-VALENT HYDROCARBON SUBSTITUENT SATISFYING A NITROGEN ATOM VALENCY OF THE IMINE GROUP. 